Abstract

The development of genetically engineered models (GEM) of epithelial ovarian cancer
(EOC) has been very successful, with well validated models representing high grade
and low grade serous adenocarcinomas and endometrioid carcinoma (EC). Most of these
models were developed using technologies intended to target the ovarian surface epithelium
(OSE), the cell type long believed to be the origin of EOC. More recent evidence has
highlighted what is likely a more prevalent role of the secretory cell of the fallopian
tube in the ontogeny of EOC, however none of the GEM of EOC have demonstrated successful
targeting of this important cell type.

The precise technologies exploited to develop the existing GEM of EOC are varied and
carry with them advantages and disadvantages. The use of tissue specific promoters
to model disease has been very successful, but the lack of any truly specific OSE
or oviductal secretory cell promoters makes the outcomes of these models quite unpredictable.
Effecting genetic change by the administration of adenoviral vectors expressing Cre recombinase may alleviate the perceived need for tissue specific promoters, however
the efficiencies of infection of different cell types is subject to numerous biological
parameters that may lead to preferential targeting of certain cell populations.

One important future avenue of GEM of EOC is the evaluation of the role of genetic
modifiers. We have found that genetic background can lead to contrasting phenotypes
in one model of ovarian cancer, and data from other laboratories have also hinted
that the exact genetic background of the model may influence the resulting phenotype.
The different genetic backgrounds may modify the biology of the tumors in a manner
that will be relevant to human disease, but they may also be modifying parameters
which impact the response of the host to the technologies employed to develop the
model.